89
Accuracy of Fine-Needle Aspiration Cytology of
Axillary Lymph Nodes in Breast Cancer Patients
A Study of 115 Cases With Cytologic-Histologic Correlation
Einas Alkuwari, MD
Manon Auger, MD
Department of Pathology, McGill University Health
Center, McGill University, Montreal, Quebec, Canada.
We thank Dr. R. P. Michel for editorial assistance
with the article.
Address for reprints: Manon Auger, MD, Depart-
ment of Pathology, McGill University, 3775 Uni-
versity Street, Room 105, Montreal, Quebec, H3A
2B4 Canada; Fax: (514) 398-7446; E-mail:
augermanon@hotmail.com
Received September 5, 2007; revision received
November 14, 2007; accepted December 7, 2007.
ª 2008 American Cancer Society
DOI 10.1002/cncr.23344
Published online 19 February 2008 in Wiley InterScience (www.interscience.wiley.com).
BACKGROUND. Fine-needle aspiration (FNA) cytology of axillary lymph nodes is a
simple, minimally invasive technique that can be used to improve preoperative
determination of the status of the axillary lymph nodes in patients with breast
cancer, thereby serving as a tool with which to triage patients for sentinel versus
full lymph node dissection procedures. The aim of the current study was to
determine the sensitivity and specificity of FNA cytology to detect metastatic
breast carcinoma in axillary lymph nodes.
METHODS. A total of 115 FNAs of axillary lymph nodes of breast cancer patients
with histologic follow-up (subsequent sentinel or full lymph node dissection)
were included in the current study. The specificity and sensitivity, as well as the
positive and negative predictive values, were calculated.
RESULTS. The positive and negative predictive values of FNA cytology of axillary
lymph nodes for metastatic breast carcinoma were 1.00 and 0.60, respectively.
The overall sensitivity of axillary lymph node FNA in all the cases studied was
65% and the specificity was 100%. The sensitivity of FNA was lower in the senti-
nel lymph node group than in the full lymph node dissection group (16% vs 88%,
respectively), which was believed to be attributable to the small size of the meta-
static foci in the sentinel lymph node group (median, 0.25 cm). All false-negative
FNAs, with the exception of 1 case, were believed to be the result of sampling
error. There was no ‘true’ false-positive FNA case in the current study.
CONCLUSIONS. FNA of axillary lymph nodes is a sensitive and very specific
method with which to detect metastasis in breast cancer patients. Because of its
excellent positive predictive value, full axillary lymph node dissection can be
planned safely instead of a sentinel lymph node dissection when a preoperative
positive FNA result is rendered. Cancer (Cancer Cytopathol) 2008;114:89–93.

2008 American Cancer Society.
KEYWORDS: fine-needle aspiration cytology, axillary lymph node, metastasis,
breast cancer, sentinel lymph node.
T he detection of metastases in axillary lymph nodes is a very im-
portant prognostic factor in breast cancer because of its impact
on subsequent management and overall survival. Different methods
are used to detect metastases in axillary lymph nodes preopera-
tively.1–19 Although some studies have used ultrasonographic ima-
ging techniques alone,2–6,12,17,18 others have used fine-needle
aspiration (FNA) cytology with or without ultrasound guidance to
improve the detection of metastases.1,7–13,15,19
FNA cytology of axillary lymph nodes is a simple, minimally
invasive technique that can be utilized as a tool with which to select
patients for sentinel versus full lymph node dissection procedures in
 10970142a, 2008, 2, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.23344 by Nat Prov Indonesia, Wiley Online Library on [26/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
90 CANCER (CANCER CYTOPATHOLOGY) April 25, 2008 / Volume 114 / Number 2

cases of breast carcinoma. Indeed, by objectively
documenting the presence of metastatic carcinoma
by preoperative FNA cytology, many patients can be
directed toward full lymph node dissection, thereby
preventing unnecessary sentinel lymph node proce-
dures and reducing the involved costs and time.
The objective of the current study was to deter-
mine the accuracy of FNA in detecting metastatic
breast carcinoma in axillary lymph nodes.
MATERIALS AND METHODS
From the database of the Department of Pathology
of the McGill University Health Center (MUHC), we
retrieved all FNAs of axillary lymph nodes (N 5 314)
performed with or without ultrasound guidance and
received at the MUHC Cytopathology Laboratory
over a 3-year period between January 1, 2004 and
December 31, 2006. From those, we identified 153
cases (48.7%) as coming from breast cancer patients
by the presence of recent, concurrent, or subsequent
breast histologic material in the same database. Of
the latter 153 axillary lymph node FNAs, 25 (16.3%)
were unsatisfactory and 13 (8.4%) had no subsequent
relevant histologic follow-up. Therefore, 115 FNAs
(75.1%) remained with histologic follow-up, either
sentinel or full axillary lymph node dissection, and
these were included in the current study. Of the total
115 axillary FNAs included in this study, 49 were per-
formed under ultrasound guidance, whereas 66 were
performed with palpation only.
For each of the 115 cases, the following data
were gathered: the original FNA cytologic diagnosis
for the axillary lymph node, the histologic diagnosis
of the primary malignancy (site of origin, size of the tu-
mor, and type and grade of breast carcinoma), the type
of diagnostic procedure for the axillary lymph node
(full lymph node dissection vs sentinel lymph node dis-
section) with the number of positive lymph nodes of
the total number of resected lymph nodes, and the
maximum size of the largest metastasis.
All the slides from the cases for which there was
a discrepancy between the cytology and the histology
(false-positive and false-negative cases) were reviewed.
The specificity, sensitivity, positive predictive values
(PPVs), and negative predictive values (NPVs) were
calculated.
RESULTS
An axillary sentinel lymph node dissection was per-
formed in 53 cases (46%), whereas a full axillary lymph
node dissection was performed in 62 cases (53.9%).
The histologic characteristics of the primary
breast carcinomas and of the axillary lymph nodes
related to the 115 cases included in this study were
as follows. The primary breast tumors included 90
cases of ductal carcinoma (78.2%), 13 cases of lobu-
lar carcinoma (11.3%), and 12 cases with mixed duc-
tal and lobular features (10.4%). According to the
Bloom-Scarff-Richardson grading for breast carci-
noma, there were 50 cases of grade 3 of 3 (43.1%), 51
cases of grade 2 of 3 (44.8%), and 14 cases of grade 1
of 3 (12.0%). The median size of the primary tumor
was 1.3 cm. The median size of the metastatic foci in
the axillary lymph nodes (with full and sentinel
lymph node dissection cases grouped together) was
1.0 cm (range, 0.09–3.0 cm); however, when broken
down by the type of axillary lymph node dissection
performed, the median size of the metastatic foci in
the sentinel lymph node group was 0.25 cm and was
1.5 cm in the full lymph node dissection group.
The breakdown of the FNA diagnoses in the 115
axillary lymph node FNAs was as follows: 49 (42.6%)
demonstrated metastatic breast carcinoma, and all
but 1 were confirmed histologically. The 1 FNA that
was not confirmed histologically (ie, all 28 axillary
lymph nodes resected were negative) was originally
believed to be a false-positive result; however, it
became clear that it actually represented a ‘false’
false-positive result. Indeed, review of the FNA
smears and the FNA cell block demonstrated unequi-
vocally malignant cells (Fig. 1, top and middle). The
discrepancy in that case was explained by the finding
that, after the performance of the axillary lymph
node FNA, the patient was treated with neoadjuvant
chemotherapy before the full lymph node dissection
was performed. Indeed, in our institution neoadju-
vant chemotherapy is typically administered to
patients with stage III breast cancer (determined
according to the Tumor, Node, Metastasis staging
system), which was the case in this particular
patient. Histologic section of 1 of the lymph nodes
demonstrated extensive scarring, presumably corre-
sponding to a ‘burnt-out’ focus of metastatic carci-
noma (Fig. 1, bottom).
Of the 66 FNAs diagnosed as benign lymph
nodes, 40 (60.6%) demonstrated no evidence of me-
tastasis in the resected lymph nodes (ie, true-nega-
tive), whereas 26 FNAs (39.4%) demonstrated
metastases in the resected lymph nodes (ie, false-
negative cases). Of the 26 false-negative FNAs, 20
(76.9%) were in the sentinel lymph node group com-
pared with only 6 cases (23%) in the full lymph node
dissection group. All false-negative FNAs, with the
exception of 1 case, were the result of sampling error
because no malignant cells were identified, even on
careful retrospective review of the FNA material.
Indeed, only 1 FNA was determined to be a false-

FNA of Axillary Lymph Nodes in Breast CA/Alkuwari and Auger
FIGURE 1. Cytology and histology from a case originally believed to be a
false-positive case, but which was later found to be a ‘false’ false-positive
case. (Top) Smear of the fine-needle aspiration (FNA) specimen of the axil-
lary lymph node demonstrating unequivocally malignant epithelial cells of
metastatic carcinoma (Papanicolaou stain, 3400). (Middle) Cell block of the
FNA of the axillary lymph node demonstrating unequivocally malignant
epithelial cells of metastatic carcinoma (H&E, 3200). (Bottom) Histology of 1
of the 28 resected axillary lymph nodes demonstrating scarring, presumably
corresponding to a ‘burnt-out’ focus of metastatic carcinoma after neoadju-
vant chemotherapy before the full lymph node dissection (H&E, 340).
10970142a, 2008, 2, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.23344 by Nat Prov Indonesia, Wiley Online Library on [26/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
91
negative result from a diagnostic standpoint (ie, diag-
nostic miss), because occasional malignant cells, ori-
ginally missed, were found on review of the FNA
slides.
The overall sensitivity and specificity of the axil-
lary lymph node FNAs in all the cases (including
both sentinel and full lymph node dissection cases)
were 65% and 100%, respectively. When considering
only the 49 ultrasound-guided FNAs, the sensitivity
was 62.5% and the specificity was 100%, whereas the
sensitivity and specificity were 67.4% and 100%,
respectively, in the 66 FNAs performed by palpation
only.
It is interesting to note that the sensitivity of
FNA was lower in the sentinel lymph node group
compared with the full lymph node dissection group
(16% vs 88%, respectively), a finding that was attrib-
utable to the small size of the metastatic foci in the
sentinel lymph node group (median of 0.25 cm vs a
median of 1.5 cm in the full lymph node dissection
group). The majority of the false-negative cases
(81.5%) was associated with lymph node metastasis
measuring \1 cm (median, 0.25 cm); in fact, the
metastatic foci were so small in 8 cases of sentinel
lymph node dissection that they were detected only
after examination of deeper levels and/or immuno-
histochemical staining of the histologic slides.
The overall PPV of the axillary lymph node FNAs
in all the cases (including both sentinel and full
lymph node dissection cases) was 1.00 and the NPV
was 0.60 at the 95% confidence interval. When con-
sidering only the 49 ultrasound-guided FNAs, the
PPV was 100% and the NPV was 58.6%, whereas the
PPV and the NPV were 100% and 62.2%, respectively,
in the 66 FNAs performed by palpation only.
DISCUSSION
Preoperative knowledge of the axillary lymph node
status for metastasis is invaluable in patients with
breast carcinoma because it affects the surgeon’s
selection of the type of axillary lymph node dissec-
tion performed, specifically sentinel versus full
lymph node dissection. Currently, in a patient known
to have at least 1 positive axillary lymph node preop-
eratively, a full axillary lymph node dissection would
be performed directly, without prior sentinel lymph
node dissection.7,11 Avoiding an unnecessary sentinel
lymph node procedure is beneficial because it is
both time-consuming and cost-consuming.7 Indeed,
the sentinel lymph node dissection procedure, which
aims at identifying the status of the first (sentinel)
lymph node draining the primary tumor within the
axilla,7 is complex and lengthy because it requires a
multidisciplinary team approach for the preoperative

92 CANCER (CANCER CYTOPATHOLOGY) April 25, 2008 / Volume 114 / Number 2
injection and detection of a blue dye and of a radio-
colloid agent. Preoperative confirmation of meta-
static breast carcinoma in an axillary lymph node
(either by FNA cytology or core needle biopsy) con-
stitutes an absolute contraindication to sentinel
lymph node dissection.20
Because determination of the axillary lymph
node status greatly affects the decision-making for
the most appropriate lymph node dissection, it is
critical to know the accuracy of the different techni-
ques used in the preoperative assessment of the axil-
lary lymph node status. To our knowledge no known
biologic tumor marker to date can predict axillary
lymph node metastases preoperatively. Different
methods have been used, including palpation, ultra-
sonography alone, and ultrasonography combined
with FNA cytology or core needle biopsy. Clinical ex-
amination alone has been shown to be inaccurate,
with a sensitivity ranging from 45.4%2 to 68%.5 For
clinical examination, de Freitas et al.5 quoted a sensi-
tivity of 68%, a specificity of 68%, a PPV of 82%, and
an NPV of 50% for a total accuracy of 68%. Approxi-
mately 15% to 60% of patients with clinically non-
palpable lymph nodes have been shown to harbor
lymph node metastases on follow-up.19
Similar to clinical examination, the accuracy of
evaluation by ultrasound only also has been shown
to be variable. Indeed, despite relying on ‘suspicious’
imaging features (such as a lymph node size [10 mm,
the absence of a fatty hilum, a hypoechoic internal
echo, a circular shape, and cortical thickening1), the
reported sensitivity of the evaluation of axillary
lymph node status by ultrasound alone has ranged
from 35%19 to 82%,10 whereas its specificity has
ranged from 73%10 to 97.9%.3 For ultrasound alone,
de Freitas et al.5 quoted a PPV of 92%, an NPV of
49%, and a total accuracy of 67%. Therefore, it
appears that ultrasonography is not sufficiently accu-
rate to replace histologic examination of the lymph
nodes for the reliable determination of metastatic
status.9
To improve the accuracy of the preoperative
assessment of axillary lymph nodes, others have
used FNA and found it to be simple, moderately
accurate, and minimally invasive, and a good triage
tool for the management of patients.1,7–13,15,19
Indeed, it has been shown that combining axillary
ultrasonography with FNA cytology of abnormal
lymph nodes can significantly reduce the number of
unnecessary sentinel lymph node procedures per-
formed by 8% to 40%, with a concomitant reduction
in healthcare costs of up to 20%.7–10,15,19
The data from the current study confirm that
FNA cytology is a useful procedure with which to
10970142a, 2008, 2, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.23344 by Nat Prov Indonesia, Wiley Online Library on [26/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
detect axillary lymph node metastases from breast
carcinoma. Indeed, we found that the overall sensi-
tivity and specificity for axillary lymph node FNAs in
all our cases were 65% and 100%, respectively,
whereas the PPV was 1.00 and the NPV was 0.60.
When considering only the ultrasound-guided FNAs
in our series, the sensitivity was 62.5%, the specificity
was 100%, the PPV was 100%, and the NPV was
58.6%, whereas when considering the FNAs per-
formed with palpation only, the sensitivity was
67.4%, the specificity was 100%, the PPV was 100%,
and the NPV was 62.2%. These results compare
favorably with those in the literature, in which the
sensitivity of ultrasound-guided FNAs for lymph
nodes ranges from 36% to 86.4%, the specificity
ranges from 95.7% to 100%, the PPV ranges from
92% to 100%, and the NPV ranges from 67%8 to
70%.7–9,11,15
The data from the current study demonstrated
that the sensitivity of lymph node FNA was lower in
the sentinel lymph node group than in the full lymph
node dissection group (ie, 16% vs 88%, respectively).
All the false-negative FNAs, with the exception of 1,
were because of sampling error. The difference in the
sensitivity of the FNA in the sentinel lymph node
group compared with the full lymph node dissection
group relates to the small size of the metastatic foci
in the sentinel lymph node group, decreasing the
likelihood of sampling the metastatic foci. Other stu-
dies have also shown that the most common cause
of false-negative cases is inadequate sampling,11 ei-
ther because of the small size of the metastases,1,3,7
the low number of lymph nodes positive for metasta-
sis,1,3,19 or failure to observe the lymph nodes during
examination of the axilla by ultrasound.1,3,18,19
Reported causes of false-positive diagnoses in
the literature are due mostly to cytologic misinter-
pretation of cells11 or inadequate sampling of the
lymph node dissection.19 In the current study, there
were no false-positive FNA cases; indeed, although 1
FNA specimen diagnosed as metastatic breast carci-
noma was not confirmed histologically (all of the 28
lymph nodes resected were found to be negative),
review of the FNA smears and cell block material
demonstrated unequivocally malignant cells. The dis-
crepancy in that case is explained by the fact the
patient was treated with neoadjuvant chemotherapy
before the full lymph node dissection was performed
and scarring was identified on the histologic section
of 1 of the lymph nodes, presumably corresponding
to a ‘burnt-out’ focus of metastatic carcinoma.
Although some studies also report an absence of
false-positive cases,13,14 others have reported false-
positive rates of 1.4% to 1.6%.7,11

FNA of Axillary Lymph Nodes in Breast CA/Alkuwari and Auger
Conclusions
FNA is a sensitive and very specific method with
which to detect metastases in the axillary lymph
nodes of patients with breast cancer. The most com-
mon cause of false-negative FNAs is sampling error
because of very small metastatic foci, especially in
the setting of sentinel lymph node dissection.
Because of its excellent positive predictive value, full
axillary lymph node dissection can be safely planned
after a positive FNA result.
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